A large number of diseases and disorders are associated with a dysfunctional immune response leading to inflammation and other clinical manifestations and pathology. It has been long established that certain disorders, such as allergies, including allergic reaction to insect bites and allergic rhinitis, skin disorders, such as psoriasis, seborrheic dermatitis, seborrheic keratosis, atopic dermatitis, acne vulgaris; solar keratosis, Crohn's disease and rheumatoid arthritis are associated with an inflammatory response. However, recent studies suggest that a greater variety of diseases and disorders have inflammatory response-based symptoms. These include such a diversity of disorder as major depression, cerebral palsy, Bell's palsy, heart disease, such as atherosclerosis, heart failure, and hypertension, Parkinson's disease, type 1 and type 2 diabetes, attention deficit hyperactivity disorder (ADHD), autism, Alzheimer's disease, stroke, inflammatory pulmonary disease, inflammatory bowel disease, endometriosis, sunburn and an ever increasing number of other presentations.
A common link between these conditions appears to be the action of cytokine signalling molecules and, in particular, pro-inflammatory cytokines that are produced in within the cell due to the action of transcription factors such as NFκB. The pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) are key players in this inflammatory/immune response. Although the evidence for the role of the pro-inflammatory response in disease processes is strong and holds a great promise therapeutically, this has not translated into a significant number of therapeutic regimes to date. The small numbers of treatments that have been used to reduce the level of the pro-inflammatory response involve the production and use of monoclonal antibodies against TNF or IL-6. Results have been encouraging, but the treatment process itself is invasive, (requiring the antibody to be injected), occasionally results in significant adverse effects and involves high treatment costs. Therefore, the general use of antibody treatment for non-life-threatening diseases not a serious option.
Methylsulphonylmethane (MSM) is an organosulphur compound, also known as DMSO2, methyl sulphone, and dimethyl sulphone. Recent in vitro evidence suggests that MSM has an anti-inflammatory effect in murine macrophages by inhibiting the release of pro-inflammatory cytokines (Kim et al (2009) Biol. Pharm. Bull 32(4): 651-656). A further study suggests that MSM may have an analgesic and anti-inflammatory effect in osteoarthritis (Usha and Naidu (2004) Clin. Drug Investig. 24(6): 353-363). A preliminary study also indicates that oral treatment with MSM at relatively high dosages (2600 mg to 5200 mg per day) may reduce symptoms associated with seasonal allergic rhinitis (Barrager et (2002) The Journal of Alternative and Complementary Medicine 8(2): 167-173).
There is also some evidence that the monosaccharide glucosamine (alone or in combination with MSM) may improve the symptoms of osteoarthritis (Usha and Naidu (2004) Clin. Drug Investig. 24(6): 353-363). In vitro studies suggest that glucosamine inhibits the synthesis of proinflammatory mediators in chondrocytes (Largo et al (2003) OsteoArthritis and Cartilage 11:290-298).
A further compound, the amino acid glycine, has been shown in in vitro studies to have an immunomodulatory action, possibly by inhibiting TNF-α production (Wheeler et al (1999) Cell. Mol. Life Sci. 56: 843-856; Spittler et al (1999) FASEB J 13: 563-571).
US2007020218 describes the use of a combination of lysine, glucosamine, chondroitin and methylsulfonylmethane, taken orally to treat psoriasis.
There remains a need for effective, non-invasive therapies that can treat conditions related to the pro-inflammatory and dysfunctional immune response, particularly therapies that have few negative side-effects and are relatively low cost.